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AIM: The aim of the present study was to identify clinical and socio-demographic factors associated with duration of untreated illness (DUI) in patients affected by panic disorder (PD). METHODS: Data were collected from patients' medical records (N = 157) of two mental health services respectively located in Milan and in Monza (Italy). Correlation analyses and analysis of variance (ANOVAs) were run to analyse the relation between DUI and quantitative/qualitative variables respectively. Statistically significant variables in uni- variate analyses were then inserted in a linear multivariable regression model (backward procedure). RESULTS: Mean DUI was 27.33 (±50.56) months. Patients with an earlier age at onset (r = -0.270; p < .01), a longer duration of illness (r = 0.483; p < .01) and who received a lifetime psychotherapy (F = 6.86; p = .01) had a longer DUI. The final global model showed that a longer DUI was associated with pre-onset poly-substance misuse (p = .05) and a longer duration of illness (p < .01). CONCLUSION: The results of our study showed that a longer DUI was predicted by clinical factors such as the presence of a pre-onset poly-substance use disorder and that delayed proper treatment can lead to a chronicization of PD, as indicated by a longer duration of illness. Further studies are needed to in-depth investigate the role of DUI in influencing the course and outcome of anxiety disorders, including PD.
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BACKGROUND: Cognitive impairment of intellectual developmental disorders (IDD) is determined by several different combinations of specific cognitive alterations. People with IDD present a rate of mental health problems that is up to 4 times higher than that of the general population. Despite this, the relationship between specific cognitive dysfunctions and co-occurring mental disorders has not been adequately studied. The aim of the present paper is to investigate the association between specific cognitive dysfunctions and specific psychiatric symptoms and syndromes in people with IDD. METHODS: One hundred and twenty adults with mild to moderate IDD living in residential facilities underwent a clinical and instrumental assessment for specific cognitive and psychopathological features. RESULTS: Participants with IDD and ASD have significantly lower scores compared to those without respect to who has not the diagnosis on the Processing Speed Index (PSI) and Perceptual Reasoning Index (PRI) on the WAIS-IV and higher time scores on the TMT A. Moreover, there is a significant association between years of hospitalisation and TMT B and TMT B A time scores; the longer a participant with IDD was hospitalised, the worse their performance on the TMT. Although not statistically significant, many psychopathological clusters showed substantial cognitive profiles. CONCLUSIONS: Although further research is needed, neuropsychological and IQ tests scores seem to be differently associated to various psychopathological conditions co-occurring with IDD, and with ASD especially. Cognitive assessment seems to support diagnosis and treatment of psychopathological co-occurrences in persons with IDD, also in consideration of indirect implications including a better knowledge of the patient's characteristics beyond IQ deficit.
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Disfunção Cognitiva , Deficiência Intelectual , Humanos , Adulto , Criança , Estudos de Coortes , Deficiências do Desenvolvimento , Psicopatologia , Hospitalização , Deficiência Intelectual/epidemiologiaRESUMO
An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far. To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers. These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.
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COVID-19 , Células-Tronco Pluripotentes Induzidas , Humanos , SARS-CoV-2 , Neurônios Dopaminérgicos , Dopamina , RNA MensageiroRESUMO
COVID-19 pandemic had a great impact on mental health, both in the general population and psychiatric patients. Little is known about the difference between these two populations in perceiving the pandemic as a traumatic event. The aim of the study was to compare psychiatric patients and healthy controls (HC) in terms of change over time of post-traumatic (PTSD) symptoms. Demographic and clinical variables were collected. Impact of Event Scale Revised (IES-R) scores were registered at T1 as lockdown period (March-April 2020) and T2 as restarting (May-June 2020). Descriptive analyses and linear regression models were performed. A total of 166 outpatients and 57 HC were recruited. Time (F = 15.76; p < 0.001) and diagnosis (F = 4.94; p < 0.001) had a significant effect on the change of IES-R scores, which resulted T1 > T2 (p < 0.001), except for subjects affected by Obsessive-Compulsive Disorder (OCD). Overall, IES-R scores were < in patients than in HC (p = 0.02), particularly in the schizophrenia (SKZ) subgroup (p < 0.001). IES-R scores of subjects with personality disorders (PDs) resulted to be > HC, although not statistically significant. The lockdown period was perceived as more traumatic than the reopening phase by both groups, with the exception of OCD patients, probably because of the clinical worsening associated with the urge of control against risks of contamination. Overall, HC reported more PTSD symptoms than psychiatric patients did, particularly SKZ ones. PD patients, in contrast, may be more vulnerable to PTSD symptoms probably as a result of poor coping skills. Together with OCD patients, subjects with PDs may need closer monitoring during the different phases of the pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04694482.
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COVID-19 , Voluntários Saudáveis , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , COVID-19/epidemiologia , COVID-19/psicologia , Pandemias , Estudos Retrospectivos , Itália/epidemiologia , Transtornos Mentais/psicologia , Ansiedade , Quarentena , Estudos de Casos e Controles , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. DESIGN AND METHODS: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. RESULTS: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). CONCLUSIONS: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.
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Testes de Coagulação Sanguínea/métodos , Síndrome de Cushing , Hidrocortisona/sangue , Trombina/análise , Trombofilia , Tromboembolia Venosa , Adrenalectomia/métodos , Adulto , Coagulação Sanguínea , Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hipofisectomia/métodos , Masculino , Período Pós-Operatório , Indução de Remissão , Medição de Risco/métodos , Trombofilia/sangue , Trombofilia/etiologia , Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
COVID-19 is a global health threat with a huge number of confirmed cases and deaths all over the world. Human-to-human transmission via respiratory droplets and contact with aerosol-infected surfaces are the major routes of virus spread. Because SARS-CoV-2 can remain in the air and on surfaces from several hours to several days, disinfection of frequently touched surfaces and critical rooms, in addition to observing individual hygiene tips, is required to reduce the virus spreading. Here we report on an investigation into the use of gaseous ozone as a potentially effective sanitizing method against the new coronavirus.
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COVID-19/prevenção & controle , COVID-19/transmissão , Desinfecção/métodos , Viabilidade Microbiana/efeitos dos fármacos , Ozônio , SARS-CoV-2/efeitos dos fármacos , Aerossóis , HumanosAssuntos
Infecções por HIV , HIV-1 , Contagem de Linfócito CD4 , Infecções por HIV/genética , HIV-1/genética , HumanosRESUMO
OBJECTIVES.: To assess admission rates to seven General Hospital Psychiatric Wards (GHPWs) located in the Lombardy Region in the 40 days after the start of Coronavirus disease 2019 (COVID-19) epidemic, compared to similar periods of 2020 and 2019. METHODS.: Anonymized data from the regional psychiatric care register have been obtained and analyzed. The seven GHPWs care for approximately 1.4 million inhabitants and have a total of 119 beds. RESULTS.: In the 40-day period (February 21-March 31, 2020) after the start of the COVID-19 epidemic in Italy, compared to a similar 40-day period prior to February 21, and compared to two 40-day periods of 2019, there has been a marked reduction in psychiatric admission rates. The reduction was explained by voluntary admissions, while there was not a noticeable reduction for involuntary admissions. The reduction was visible for all diagnostic groups, except for a group of 'Other' diagnoses, which includes anxiety disorders, neurocognitive disorders, etc. CONCLUSIONS.: Large-scale pandemics can modify voluntary admission rates to psychiatric facilities in the early phases following pandemic onset. We suggest that the reduction in admission rates may be due to fear of hospitals, seen as possible sites of contagion, as well as to a change in thresholds of behavioral problems acting as a trigger for admission requests from family relatives or referrals from treating clinicians. It is unclear from the study whether the reduction in admissions was contributed to most by the current pandemic or the lockdown imposed due to the pandemic.
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COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Humanos , Itália , Transtornos Mentais/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Sistema de RegistrosRESUMO
Time-varying metasurfaces are emerging as a powerful instrument for the dynamical control of the electromagnetic properties of a propagating wave. Here we demonstrate an efficient time-varying metasurface based on plasmonic nano-antennas strongly coupled to an epsilon-near-zero (ENZ) deeply subwavelength film. The plasmonic resonance of the metal resonators strongly interacts with the optical ENZ modes, providing a Rabi level spitting of â¼30%. Optical pumping at frequency ω induces a nonlinear polarization oscillating at 2ω responsible for an efficient generation of a phase conjugate and a negative refracted beam with a conversion efficiency that is more than 4 orders of magnitude greater compared to the bare ENZ film. The introduction of a strongly coupled plasmonic system therefore provides a simple and effective route towards the implementation of ENZ physics at the nanoscale.
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BACKGROUND: This prospective cohort study aimed at evaluating patterns of polypharmacy and aggressive and violent behavior during a 1-year follow-up in patients with severe mental disorders. METHODS: A total of 340 patients (125 inpatients from residential facilities and 215 outpatients) were evaluated at baseline with the Structured Clinical Interview for DSM-IV Axis I and II, Brief Psychiatric Rating Scale, Specific Levels of Functioning scale, Brown-Goodwin Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Barratt Impulsiveness Scale, and State-Trait Anger Expression Inventory-2. Aggressive behavior was rated every 15 days with the Modified Overt Aggression Scale and treatment compliance with the Medication Adherence Rating Scale. RESULTS: The whole sample was prescribed mainly antipsychotics with high levels of polypharmacy. Clozapine prescription and higher compliance were associated with lower levels of aggressive and violent behavior. Patients with a history of violence who took clozapine were prescribed the highest number of drugs. The patterns of cumulative Modified Overt Aggression Scale mean scores of patients taking clozapine (n = 46), other antipsychotics (n = 257), and no antipsychotics (n = 37) were significantly different (P = .001). Patients taking clozapine showed a time trend at 1-year follow-up (24 evaluations) indicating a significantly lower level of aggressive behavior. Patient higher compliance was also associated with lower Modified Overt Aggression Scale ratings during the 1-year follow-up. CONCLUSION: Both inpatients and outpatients showed high levels of polypharmacy. Clozapine prescription was associated with lower Modified Overt Aggression Scale ratings compared with any other antipsychotics or other psychotropic drugs. Higher compliance was associated with lower levels of aggressive and violent behavior.
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Agressão/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Padrões de Prática Médica/tendências , Psicotrópicos/efeitos adversos , Violência , Adolescente , Adulto , Estudos Transversais , Prescrições de Medicamentos , Uso de Medicamentos/tendências , Feminino , Humanos , Itália , Masculino , Adesão à Medicação , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Polimedicação , Estudos Prospectivos , Fatores de Tempo , Adulto JovemRESUMO
Two-color terahertz (THz) generation is a field-matter process combining an optical pulse and its second harmonic. Its application in condensed matter is challenged by the lack of phase matching among multiple interacting fields. Here, we demonstrate phase-matching-free two-color THz conversion in condensed matter by introducing a highly resonant absorptive system. The generation is driven by a third-order nonlinear interaction localized at the surface of a narrow-band-gap semiconductor, and depends directly on the relative phase between the two colors. We show how to isolate the third-order effect among other competitive THz-emitting surface mechanisms, exposing the general features of the two-color process.
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OBJECTIVES: Despite recent pharmacological progress, memory impairment is still frequently reported in people living with HIV. We aimed to conduct a systematic literature review investigating the presence of impairment of (sub)components of memory function in patients prescribed highly active antiretroviral therapy (ART). METHODS: We adopted a cognitive neuropsychological model of memory function as the theoretical framework, distinguishing between a short-term working memory component and a long-term component of memory, along with their specific (sub)components. We systematically searched for the presence of impairment of each (sub)component in the selected papers. Careful consideration was given to study design and methods and control of covariates. RESULTS: Only the central executive component of working memory has been consistently reported to be impaired in HIV infection. The other two (sub)components, namely the phonological loop and the visuospatial sketchpad, were unimpaired. Discordant results have been obtained as to verbal and visual episodic memory, as some authors reported an association with HIV infection, whereas others did not. There is little evidence for semantic memory deficit in HIV infection, while there are suggestions that the neural substrate of implicit memory may be damaged by the effects of HIV infection and inflammation. Most studies in this area have been conducted in small samples and with poor control for covariates. Thus, conclusions regarding the association of memory dysfunction with HIV infection are hampered by methodological issues such as selection bias and unmeasured confounding. CONCLUSIONS: The task remains for future research to ascertain the impact of HIV infection on memory function.
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Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Transtornos da Memória/etiologia , Feminino , Infecções por HIV/psicologia , Humanos , Masculino , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo , Testes Neuropsicológicos , Estudos Observacionais como Assunto , Cooperação e Adesão ao TratamentoRESUMO
OBJECTIVES: To identify the variables that are associated with persistence to Aripiprazole-Long Acting (A-LAI), in adult patients with schizophrenia. METHODS: Observational, retrospective, non-interventional study involving 261 patients with schizophrenia. RESULTS: Eighty-six percent of study subjects were persistent for at least 6 months. All subjects with baseline CGI-S of 1 or 2, 95% of subjects with CGI-S of 3, 86% with CGI-S of 4, 82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7 were persistent. A-LAI treatment continuation rate was higher in patients with: 1) baseline CGI scoreâ¯≤â¯4; 2) schizophrenia dimension (LDPS) mania scoreâ¯≤â¯5; 3) psychotic spectrum schizoid scoreâ¯≤â¯11. CONCLUSIONS: A relatively high number of patients (nâ¯=â¯225, 86%) were persistent to A-LAI for at least 6 months. Not surprisingly, very severe patients were more unlikely to be persistent. However, it is noteworthy that a large number of subjects with high CGI score at the time when A-LAI was started (82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7) were persistent. Larger, controlled, prospective and longer studies are warranted.
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Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Itália , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Essentials Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. EDS is associated with an increased risk of bleeding. EDS patients have platelet function abnormalities, whose severity correlates with bleeding risk. SUMMARY: Background Ehlers-Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking. Objective To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS). Methods The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities. Results Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.87-7.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32-20.45) when more than three abnormalities were detected. Conclusions Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS.
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Plaquetas/metabolismo , Síndrome de Ehlers-Danlos/complicações , Hemorragia/etiologia , Hemostasia , Adulto , Testes de Coagulação Sanguínea/normas , Síndrome de Ehlers-Danlos/sangue , Síndrome de Ehlers-Danlos/diagnóstico , Feminino , Hemorragia/sangue , Hemorragia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/normas , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemAssuntos
Antioxidantes , Transtorno Depressivo , Depressão , Humanos , Estresse Oxidativo , Ácido ÚricoRESUMO
This corrects the article DOI: 10.1038/ncomms15829.
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Nanophotonics and metamaterials have revolutionized the way we think about optical space (É,µ), enabling us to engineer the refractive index almost at will, to confine light to the smallest of the volumes, and to manipulate optical signals with extremely small footprints and energy requirements. Significant efforts are now devoted to finding suitable materials and strategies for the dynamic control of the optical properties. Transparent conductive oxides exhibit large ultrafast nonlinearities under both interband and intraband excitations. Here we show that combining these two effects in aluminium-doped zinc oxide via a two-colour laser field discloses new material functionalities. Owing to the independence of the two nonlinearities, the ultrafast temporal dynamics of the material permittivity can be designed by acting on the amplitude and delay of the two fields. We demonstrate the potential applications of this novel degree of freedom by dynamically addressing the modulation bandwidth and optical spectral tuning of a probe optical pulse.
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The morbidity and mortality of community-acquired pneumonia (CAP) are still elevated and two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response. Adjuvants, including corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects but their efficacy is only partial. We examined the immunomodulatory activity of Pidotimod (PDT), a synthetic dipeptide molecule in adult patients hospitalized for CAP. Sixteen patients with a diagnosis of CAP and a PSI score III or IV and/or a CURB-65 0-2 were randomized to receive either levofloxacin 500 mg b.i.d. alone or levofloxacin plus PDT (800mg, 2 daily doses). Blood samples were drawn at baseline (T0), before initiation of therapy, as well as 3 (T3), and 5 (T5) days after initiation of therapy. Immunologic and clinical parameters were analyzed at each time point. Supplementation of antibiotic therapy with PDT resulted in an upregulation of antimicrobial and of immunomodulatory proteins as well as in an increased percentage of Toll like receptor (TLR)2- and TLR4, and of CD80- and CD86-expressing immune cells. Notably, Pidotimod supplementation was also associated with a robust reduction of TNFα-producing immune cells. No significant differences were observed in clinical parameters. These results confirm that supplementation of antibiotic therapy with Pidotimod in patients with CAP results in a potentially beneficial modulation of innate immunity.
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Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia/tratamento farmacológico , Ácido Pirrolidonocarboxílico/análogos & derivados , Tiazolidinas/administração & dosagem , Infecções Comunitárias Adquiridas/imunologia , Feminino , Hospitalização , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pneumonia/imunologia , Estudos Prospectivos , Ácido Pirrolidonocarboxílico/administração & dosagem , Ácido Pirrolidonocarboxílico/farmacologia , Tiazolidinas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Sarcopenia is the progressive loss of muscle mass and strength that occurs with advancing age and plays a pivotal role in the causal pathway leading to frailty, disability and, eventually, to death among older persons. As oxidative damage of muscle proteins has been shown to be a relevant contributory factor, in this study we hypothesized that uric acid (UA), a powerful endogenous antioxidant, might exert a protective effect on muscle function in the oldest old and we tested our hypothesis in a group of nonagenarians who participated in the Mugello Study. METHODS: 239 subjects, 73 men and 166 women, mean age 92.8years±SD 3.1, underwent the assessment of UA serum level and isometric handgrip strength, a widely used clinical measure of sarcopenia. RESULTS: Mean UA serum level was 5.69mg/dL±SD 1.70 and mean handgrip strength was 15.0kg±SD 6.9. After adjusting for relevant confounders, higher UA serum levels remained independent positive predictors of isometric handgrip strength (ß 1.24±SE(ß) 0.43, p=0.005). CONCLUSION: Our results show that higher UA serum levels are associated with better muscle function in the oldest old and, accordingly, might slow down the progression of sarcopenia.